Postoperative Radiotherapy For Prostate Cancer Research Articles

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61-69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1-10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688-1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4-82·5) in the no ADT group and 80·4% (76·6-83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population. Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society.

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60-69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0-10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612-0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6-75·7) in the short-course ADT group and 78·1% (74·2-81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society.

10-yr Results of Moderately Hypofractionated Postoperative Radiotherapy for Prostate Cancer Focused on Treatment Related Toxicity

IntroductionTo retrospectively report long term outcomes following postoperative hypofractionated radiotherapy (RT) for prostate cancer, emphasizing treatment related toxicity. Material and MethodsPatients for whom adjuvant or salvage RT was indicated after prostatectomy were treated with a course of moderate hypofractionation consisting in the delivery of 62.5 Gy in 25 fractions (2.5 Gy per fraction) on the prostate bed in 5 consecutive weeks (EQD21.5 = 70 Gy) by means of 3D-CRT in most of them. Androgen deprivation therapy (ADT) was allowed at physician's discretion. Patients were evaluated for urinary and rectal complications according to the Common Terminology Criteria for Adverse Events v4 (CTCAE v.4). Overall survival (OS), biochemical recurrence free survival (bRFS), and metastasis-free survival (MFS) were estimated using the Kaplan–Meier method. ResultsOne hundred and ten patients with a median age of 67 years (range 51-78) were enrolled. The majority of them (82%) had adverse pathologic features only, while 31 (28%) had early biochemical relapse. Median PSA level before RT was 0.12 ng/mL (range 0-9 ng/mL). Median time from surgery was 4 months (range 1-136 months). Twenty-eight patients (25.4%) also received ADT. At a median follow up of 103 months (range 19-138 months), late Grade 3 and Grade 4 rectal toxicity were 0.9% (1 case of hematochezia) and 0.9% (1 case of fistula), respectively, while late Grade 3 GU side effects (urethral stenosis) occurred in 9 cases (8%). No late Grade 4 events were observed, respectively. Ten-year OS, b-RFS and MFS were 77.3% (95%CI: 82.1%-72.5%), 53.3% (95%CI: 59.9%-47.6%), and 76.7% (95%CI: 81.2%-72.2%), respectively. ConclusionOur study provides long term data that a shortened course of postoperative RT is as safe and effective as a long course of conventionally fractionated RT and would improve patients’ convenience and significantly reduce RT department workloads.

ESTROACROP guideline on prostate bed delineation for postoperative radiotherapy in prostate cancer.

Radiotherapy to the prostate bed is a potentially curative salvage option after radical prostatectomy. Although prostate bed contouring guidelines are available in the literature, important variabilities exist. The objective of this work is to provide a contemporary consensus guideline for prostate bed delineation for postoperative radiotherapy. An ESTRO-ACROP contouring consensus panel consisting of 11 radiation oncologists and one radiologist, all with known subspecialty expertise in prostate cancer, was established. Participants were asked to delineate the prostate bed clinical target volumes (CTVs) in 3 separate clinically relevant scenarios: adjuvant radiation, salvage radiation with PSA progression, and salvage radiation with persistently elevated PSA. These cases focused on the presence of positive surgical margin, extracapsular extension, and seminal vesicles involvement. None of the cases had radiographic evidence of local recurrence on imaging. A single computed tomography (CT) dataset was shared via FALCON platform and contours were performed using EduCaseTM software. Contours were analyzed qualitatively using heatmaps which provided a visual assessment of controversial regions and quantitatively analyzed using Sorensen-Dice similarity coefficients. Participants also answered case-specific questionnaires addressing detailed recommendations on target delineation. Discussions via electronic mails and videoconferences for final editing and consensus were performed. The mean CTV for the adjuvant case was 76cc (SD=26.6), salvage radiation with PSA progression was 51.80cc (SD=22.7), and salvage radiation with persistently elevated PSA 57.63cc (SD=25.2). Compared to the median, the mean Sorensen-Dice similarity coefficient for the adjuvant case was 0.60 (SD 0.10), salvage radiation with PSA progression was 0.58 (SD=0.12), and salvage radiation with persistently elevated PSA 0.60 (SD=0.11). A heatmap for each clinical scenario was generated. The group agreed to proceed with a uniform recommendation for all cases, independent of the radiotherapy timing. Several controversial areas of the prostate bed CTV were identified based on both heatmaps and questionnaires. This formed the basis for discussions via videoconferences where the panel achieved consensus on the prostate bed CTV to be used as a novel guideline for postoperative prostate cancer radiotherapy. Variability was observed in a group formed by experienced genitourinary radiation oncologists and a radiologist. A single contemporary ESTRO-ACROP consensus guideline was developed to address areas of dissonance and improve consistency in prostate bed delineation, independent of the indication.There is important variability in existing contouring guidelines for postoperative prostate bed (PB) radiotherapy (RT) after radical prostatectomy. This work aimed at providing a contemporary consensus guideline for PB delineation. An ESTRO ACROP consensus panel including radiation oncologists and a radiologist, all with known subspecialty expertise in prostate cancer, delineated the PB CTV in 3 scenarios: adjuvant RT, salvage RT with PSA progression, and salvage RT with persistently elevated PSA. None of the cases had evidence of local recurrence. Contours were analysed qualitatively using heatmaps for visual assessment of controversial regions and quantitatively using Sorensen-Dice coefficient. Case-specific questionnaires were also discussed via e-mails and videoconferences for consensus. Several controversial areas of the PB CTV were identified based on both heatmaps and questionnaires. This formed the basis for discussions via videoconferences. Finally, a contemporary ESTRO-ACROP consensus guideline was developed to address areas of dissonance and improve consistency in PB delineation, independent of the indication.

SP-0998 ESTRO-ACROP guideline on prostate bed delineation for postoperative radiotherapy in prostate cancer

SP-0998 ESTRO-ACROP guideline on prostate bed delineation for postoperative radiotherapy in prostate cancer

Hypofractionated Postoperative Radiotherapy in Prostate Cancer with Ialuril Soft Gels®: Toxicity and Efficacy Analysis on a Retrospective Series of 305 Patients.

AimTo evaluate the impact of Ialuril soft Gels® (HA) in reducing acute genito-urinary (GU) toxicity in patients treated with adjuvant or salvage radiotherapy for a prostate cancer relapse.Material and MethodsThe data of 305 patients were retrospectively collected. One hundred and five patients underwent adjuvant radiotherapy (aRT), while 200 a salvage treatment (sRT). GU toxicity was evaluated according to CTCAE v5.0. Every patient received RT combined with HA.ResultsGrade 1–2 GU toxicity during RT was represented by: urgency (36%), dysuria (23%), increased urinary frequency (12.1%), and urinary retention (11.8%). Nevertheless, the majority of symptoms were present at the baseline. Grade 3 severe toxicity was represented by 10 (3.2%) cases of incontinence and 3 (1%) cases of urgency. The incidence of any-grade RT-related GU toxicity was significantly higher in the aRT group than the salvage group (esRT + sRT) (83.8% versus 64.5%). When comparing the incidence of any-grade RT-related GU toxicity in the aRT, esRT, and sRT groups we observed a significant correlation favoring sRT, over esRT, and aRT.ConclusionPostoperative hypofractionated radiotherapy is safe and not correlated with increase of unexpected toxicity when administered with oral hyaluronic acid. A prospective study is necessary to confirm these results.

Assessing radiation dose for postoperative radiotherapy in prostate cancer: Real world data.

BACKGROUNDApproximately 30% of patients with localized prostate cancer (PCa) who undergo radical prostatectomy will develop biochemical recurrence. In these patients, the only potentially curative treatment is postoperative radiotherapy (PORT) with or without hormone therapy. However, the optimal radiotherapy dose is unknown due to the limited data available. AIMTo determine whether the postoperative radiotherapy dose influences biochemical failure-free survival (BFFS) in patients with PCa. METHODSRetrospective analysis of patients who underwent radical prostatectomy for PCa followed by PORT-either adjuvant radiotherapy (ART) or salvage radiotherapy (SRT)-between April 2002 and July 2015. From 2002 to 2010, the prescribed radiation dose to the surgical bed was 66-70 Gy in fractions of 2 Gy; from 2010 until July 2015, the prescribed dose was 70-72 Gy. Patients were grouped into three categories according to the total dose administered: 66-68 Gy, 70 Gy, and 72 Gy. The primary endpoint was BFFS, defined as the post-radiotherapy prostate-specific antigen (PSA) nadir + 0.2 ng/mL. Secondary endpoints were overall survival (OS), cancer-specific survival (CSS), and metastasis-free survival (MFS; based on conventional imaging tests). Treatment-related genitourinary (GU) and gastrointestinal (GI) toxicity was evaluated according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. Finally, we aimed to identify potential prognostic factors. BFFS, OS, CSS, and MFS were calculated with the Kaplan-Meier method and the log-rank test. Univariate and multivariate Cox regression models were performed to explore between-group differences in survival outcome measures.RESULTSA total of 301 consecutive patients were included. Of these, 93 (33.6%) received ART and 186 (66.4%) SRT; 22 patients were excluded due to residual macroscopic disease or local recurrence in the surgical bed. In this subgroup (n = 93), 43 patients (46.2%) were Gleason score (GS) ≤ 6, 44 (47.3%) GS 7, and 6 (6.5%) GS ≥ 8; clinical stage was cT1 in 51 (54.8%), cT2 in 35 (39.3%), and cT3 in one patient (1.1%); PSA was < 10 ng/mL in 58 (63%) patients, 10-20 ng/mL in 28 (30.6%), and ≥ 20 ng/mL in 6 (6.4%) patients. No differences were found in BFFS in this patient subset versus the entire cohort of patients (P = 0.66). At a median follow-up of 113 months (range, 4-233), 5- and 10-year BFFS rates were 78.8% and 73.7%, respectively, with OS rates of 93.3% and 81.4%. The 5-year BFFS rates in three groups were as follows: 69.6% (66-68 Gy), 80.5% (70 Gy) and 82.6% (72 Gy) (P = 0.12):the corresponding 10-year rates were 63.9%, 72.9%, and 82.6% (P = 0.12), respectively. No significant between-group differences were observed in MFS, CSS, or OS. On the univariate analysis, the following variables were significantly associated with BFFS: PSA at diagnosis; clinical stage (cT1 vs cT2); GS at diagnosis; treatment indication (ART vs SRT); pre-RT PSA levels; and RT dose 66 -68 Gy vs. 72 Gy (HR: 2.05; 95%CI: 1.02-4.02, P = 0.04). On the multivariate analysis, the following variables remained significant: biopsy GS (HR: 2.85; 95%CI: 1.83-4.43, P < 0.001); clinical stage (HR: 2.31; 95%CI: 1.47-4.43, P = 0.01); and treatment indication (HR: 4.11; 95%CI: 2.06-8.17, P < 0.001). Acute grade (G) 1 GU toxicity was observed in 11 (20.4%), 17 (19.8%), and 3 (8.3%) patients in each group (66-68 Gy, 70 Gy and 72 Gy), respectively (P = 0.295). Acute G2 toxicity was observed in 2 (3.7%), 4 (4.7%) and 2 (5.6%) patients, respectively (P = 0.949). Acute G1 GI toxicity was observed in 16 (29.6%), 23 (26.7%) and 2 (5.6%) patients in each group, respectively (P = 0.011). Acute G2 GI toxicity was observed in 2 (3.7%), 6 (6.9%) and 1 (2.8%) patients, respectively (P = 0.278). No cases of acute G3 GI toxicity were observed.CONCLUSIONThe findings of this retrospective study suggest that postoperative radiotherapy dose intensification in PCa is not superior to conventional radiotherapy treatment.

OC-0608 Phase II trial of hypofractionated postoperative radiotherapy in prostate cancer: NCT02192788

OC-0608 Phase II trial of hypofractionated postoperative radiotherapy in prostate cancer: NCT02192788

Post-Operative Radiotherapy in Prostate Cancer: Is It Time for a Belt and Braces Approach?

Approximately 30% of patients treated with radical prostatectomy (RP) for prostate cancers experience biochemical recurrence (BCR). Post-operative radiation therapy (RT) can be either offered immediately after the surgery in case of aggressive pathological features or proposed early if BCR occurs. Until recently, little data were available regarding the optimal RT timing, protocol, volumes to treat, and the benefit of adding androgen deprivation therapies to post-operative RT. In this review, we aim to pragmatically discuss current literature data on these points. Early salvage RT appears to be the optimal post-operative approach, improving oncological outcomes especially with low prostate-specific antigen (PSA) levels, as well as sparing several unnecessary adjuvant treatments. The standard RT dose is still 64–66 Gy to the prostate bed in conventional fractionation, but hypofractionation protocols are emerging pending on late toxicity data. Several scientific societies have published contouring atlases, even though they are heterogeneous and deserve future consensus. During salvage RT, the inclusion of pelvic lymph nodes is also controversial, but preliminary data show a possible benefit for PSA > 0.34 ng/ml at the cost of increased hematological side effects. Concomitant ADT and its duration are also discussed, possibly advantageous (at least in terms of metastasis-free survival) for PSA rates over 0.6 ng/ml, taking into account life expectancy and cardiovascular comorbidities. Intensified regimens, for instance, with new-generation hormone therapies, could further improve outcomes in carefully selected patients. Finally, recent advances in molecular imaging, as well as upcoming breakthroughs in genomics and artificial intelligence tools, could soon reshuffle the cards of the current therapeutic strategy.

Postoperative radiotherapy in prostate cancer: Dose and volumes

Approximately thirty percent of patients experience biochemical recurrence after radical prostatectomy for prostate cancer. Early salvage radiotherapy has recently become a standard of care in this setting. The purpose of this review is first to summarize current knowledge in terms of dose to the prostate bed in light of the recent SAKK 09/10 randomized phase III trial results. The evidence on moderate hypofractionation will also be discussed whereas extreme hypofractionation remains highly investigational. Regarding target volumes, several different guidelines have been published to address the need for standardization of postoperative target delineation. The recent GFRU (Groupe Francophone de Radiothérapie Urologique) recommendations could represent an international consensus.

A deep learning-based framework for segmenting invisible clinical target volumes with estimated uncertainties for post-operative prostate cancer radiotherapy.

In post-operative radiotherapy for prostate cancer, precisely contouring the clinical target volume (CTV) to be irradiated is challenging, because the cancerous prostate gland has been surgically removed, so the CTV encompasses the microscopic spread of tumor cells, which cannot be visualized in clinical images like computed tomography or magnetic resonance imaging. In current clinical practice, physicians' segment CTVs manually based on their relationship with nearby organs and other clinical information, but this allows large inter-physician variability. Automating post-operative prostate CTV segmentation with traditional image segmentation methods has yielded suboptimal results. We propose using deep learning to accurately segment post-operative prostate CTVs. The model proposed is trained using labels that were clinically approved and used for patient treatment. To segment the CTV, we segment nearby organs first, then use their relationship with the CTV to assist CTV segmentation. To ease the encoding of distance-based features, which are important for learning both the CTV contours' overlap with the surrounding OARs and the distance from their borders, we add distance prediction as an auxiliary task to the CTV network. To make the DL model practical for clinical use, we use Monte Carlo dropout (MCDO) to estimate model uncertainty. Using MCDO, we estimate and visualize the 95% upper and lower confidence bounds for each prediction which informs the physicians of areas that might require correction. The model proposed achieves an average Dice similarity coefficient (DSC) of 0.87 on a holdout test dataset, much better than established methods, such as atlas-based methods (DSC<0.7). The predicted contours agree with physician contours better than medical resident contours do. A reader study showed that the clinical acceptability of the automatically segmented CTV contours is equal to that of approved clinical contours manually drawn by physicians. Our deep learning model can accurately segment CTVs with the help of surrounding organ masks. Because the DL framework can outperform residents, it can be implemented practically in a clinical workflow to generate initial CTV contours or to guide residents in generating these contours for physicians to review and revise. Providing physicians with the 95% confidence bounds could streamline the review process for an efficient clinical workflow as this would enable physicians to concentrate their inspecting and editing efforts on the large uncertain areas.

Prognostic factors in postoperative radiotherapy for prostate cancer - tertiary center experience.

BackgroundThe aim of the study was to analyse the prognostic factors in postoperative prostate cancer irradiation and develop a nomogram for disease-free survival (DFS).Patients and methodsThis retrospective study included 236 consecutive prostate cancer patients who had radical prostatectomy followed by radiotherapy (RT) at a single tertiary institution between 2009 and 2014. The main outcome was DFS analysed through uni- and multivariable analysis, Kaplan-Meier curves, log-rank testing, recursive partitioning analysis, and nomogram development.ResultsThe median follow up was 62.3 (interquartile range [IQR] 38.1–79) months. The independent clinical factors associated with increased risk of recurrence or progression in the multivariate analysis (MVA) were prostate-specific antigen (PSA) level before RT, pT3 characteristic, and local failure as salvage indication. The value of PSA nadir had a significant impact on the risk of biochemical failure. Biochemical control and DFS were significantly different depending on treatment indication (p < 0.0001). The recursive partitioning analysis highlighted the importance of the PSA level before RT, Gleason Grade Group, PSA nadir, and local failure as a treatment indication. Finally, the nomogram for DFS was developed and is available online at https://apps.konsta.com.pl/app/prostate-salvage-dfs/.ConclusionsThe Pre-RT PSA level, pT3 characteristic and local failure as salvage indication are pivotal prognostic factors associated with increased risk of recurrence or progression. The Gleason grade group of 4–5 and PSA nadir value allow for further risk stratification. The treatment outcomes in postoperative prostate cancer irradiation are significantly different depending on treatment indication. An online nomogram comprising of both pre-treatment and current data was developed allowing for visualization of changes in prognosis depending on clinical data.

Consequential late effects up to >10 years following primary and postoperative radiotherapy for prostate cancer

Consequential late effects up to >10 years following primary and postoperative radiotherapy for prostate cancer

PO-1159: Toxicity Profile in Postoperative Radiotherapy for Prostate Cancer with Moderate Hypofractionation

PO-1159: Toxicity Profile in Postoperative Radiotherapy for Prostate Cancer with Moderate Hypofractionation

Consequential Late Effects up to 10 years Following Primary and Postoperative Radiotherapy for Prostate Cancer

To evaluate the impact of acute toxicity on chronic problems following primary (pRT) and postoperative radiotherapy (opRT) for prostate cancer. Patients treated in the years 2003-2008 were surveyed prospectively using a validated questionnaire (EPIC, Expanded Prostate Cancer Index Composite) before the beginning of RT, at the last day, two months, 1-3 years, 5-8 years and 9-13 years after the end of RT. A score difference of 5 points is regarded as clinically significant, >20 points as a clinically large quality of life (QoL) change. Only patients treated up to 70.2-72Gy (pRT) and 66.0-66.6Gy (opRT) in 1.8-2.0Gy fractions were included. Patients were required to respond to the questionnaire before and at the end of RT, additionally at least one questionnaire >1 year after RT, resulting in 287 patients (n = 185 pRT and n = 102 opRT). The response rate to the questionnaire after 1-3 years was 85% (n = 245), after 5-8 70% (n = 201) and after 9-13 years 55% (n = 157). Significant differences before the start of RT between pRT and opRT were lower urinary (mean bother score of 87 vs. 82; p = 0.02) and sexual (mean bother score of 61 vs. 39; p<0.01) scores for opRT. However, larger changes at the end of RT were found for pRT (urinary score: 21 vs. 13 points; p<0.01; sexual score: 11 vs. -2 Punkte; p<0.01; negative change = QoL improvement). After 10 years, urinary scores declined less (5 vs. 14 points; p = 0.04), sexual scores declined more (18 vs. -2 points; p = 0.01) following pRT vs. opRT. For patients with a bother score decline >20 points in the bowel domain (Bdiff>20) and urinary domain (Udiff>20) at the last day of RT, the respective bowel baseline scores were similar both for pRT and opRT, urinary baseline scores only for opRT. However, patients with pRT and Udiff>20 had significantly higher baseline scores (85 vs. 79; p<0.01). For patients with Bdiff >20, both the difference in relation to baseline levels and the absolute bother scores 10 years after RT remained significantly worse in comparison to patients with smaller acute changes (71 vs. 93 10 years after pRT; p<0.01; 82 vs. 91 after opRT; p = 0.07). The same effect was found for patients with Udiff>20 in the urinary domain, statistically significant up to 5 years after pRT, but only up to 2 months after opRT. In comparison to opRT, significantly larger acute, but smaller chronic urinary changes resulted. Acute toxicity during radiotherapy has a significant impact on chronic problems as consequential late effects, especially in the bowel domain. These acute bowel score changes cannot be predicted by baseline problems before the beginning of treatment.

Associations of Stromal Infiltration with Prognosis and Response to Postoperative Radiotherapy in Prostate Cancer

Associations of Stromal Infiltration with Prognosis and Response to Postoperative Radiotherapy in Prostate Cancer

The value of a bladder-filling protocol for patients with prostate cancer who receive post-operative radiation: results from a prospective clinical trial

Background and purpose: This study compares two different strategies for maintaining a constant bladder volume during a course of postoperative radiotherapy in prostate cancer. In addition, we studied how changes in bladder filling affect the clinical target volume (CTV) and the coverage hereof.Material and Methods: Twenty-nine patients with PSA-relapse after radical prostatectomy were divided into two groups: voiding and drinking 300 ml 1 hour before treatment (Group 1); and maintained a comfortably filled bladder (Group 2). The bladder volumes were calculated based on the planning CT (pCT) and a weekly Cone Beam CT (CBCT) during the treatment period. Furthermore, the variability of bladder extension was analyzed and correlated to the volume of the bladder covered with the 95% of the dose (V95%,bladder).Results: The estimated median bladder volumes were 120 ml (95% CI: (93, 154)) and 123 ml (95% CI: (98, 155)) in groups 1 and 2, respectively. The intra-individual variation in bladder volume, assessed as the standard deviation, was 64 ml (95% CI: (46, 105)) in Group 1 and 61 (95% CI: (45, 94)) ml in Group 2. Increasing the bladder volume extended the bladder cranially while the caudal extension was almost constant. The correlation between bladder volume and V95%,bladder was 3.5 ml per 100 ml in group 1 and 1.2 ml per 100 ml in group 2 with no significant difference.Conclusions: The intention to maintain a constant volume for the bladder is not fulfilled with either of the protocols in this study, and changes in bladder volumes does not seem to affect the position, or the coverage of the CTV.

A preliminary toxicity study of different dose fractionation regimens in postoperative radiotherapy for prostate cancer

Objective To compare the toxicity between different dose fractionation regimens in postoperative radiotherapy for prostate cancer. Methods Patients with prostate cancer who received postoperative radiotherapy with moderate hypo-fractionation (62.75 Gy in 25 fractions, 2.51 Gy per fraction) or conventional fractionation (72 Gy in 36 fractions, 2 Gy per fractions) in our hospital from 2011 to 2017 were enrolled as subjects. All patients received intensity-modulated radiotherapy and daily cone-beam computed tomography image-guided radiotherapy. According to the propensity score matching (PSM) method, 35 patients treated with moderately hypo-fractionated radiotherapy were matched to 35 patients treated with conventionally fractionated radiotherapy based on age, irradiated volume, hormonal therapy, interval between surgery and radiotherapy, and comorbidities (diabetes and hypertension). Toxicity was evaluated according to Radiation Therapy Oncology Group criteria. Comparison was made by the Fisher′s exact probability test. Results One hundred and thirteen patients, consisting of forty-one in moderate hypo-fractionation group and seventy-two in conventional fractionation group, were enrolled as subjects. The median follow-up time in the two groups was 5.6 and 45.0 months, respectively. There were no significant differences in incidence rates of grade 2 acute gastrointestinal (GI) or genitourinary (GU) toxicity between the two groups (7% vs. 7%, P=1.000; 15% vs. 17%, P=0.847). After PSM, there were still no significant differences in incidence rates of grade 2 acute GI or GU toxicity between the two groups (9% vs. 11%, P=0.814; 14% vs. 11%, P=0.670). None of patients reported ≥grade 3 GI or GU toxicity. Conclusions Preliminary results show that moderate hypo-fractionation, compared with conventional fractionation, does not increase the risk of acute GI or GU toxicity in patients undergoing postoperative radiotherapy for prostate cancer. Key words: Prostate neoplasms/postoperative radiotherapy; Radiotherapy, moderately hypo-fractionated; Radiotherapy, conventionally fractionated

Contemporary role of postoperative radiotherapy for prostate cancer.

While radical prostatectomy (RP) has provided long-term disease control for the majority of patients with localized prostate cancer (CaP), nearly 30% of all surgical patients have disease progression. For high-risk patients, more than half of men experience disease recurrence within 10 years. Postoperative radiotherapy is the only known potentially curative treatment for a large number of patients following prostatectomy. Lately, there have been several advances with the potential to improve outcomes for patients undergoing postoperative radiotherapy. This article will give an overview of the existing literature and current controversies on: (I) timing of postoperative radiation; (II) use of concomitant androgen deprivation therapy; (III) optimal dose to the prostate bed; (IV) use of hypofractionation; (V) elective treatment of the pelvic lymph nodes; (VI) novel imaging modalities, and (VII) genomic biomarkers.

Volumetric and dosimetric comparison of organs at risk between the prone and supine positions in postoperative radiotherapy for prostate cancer

BackgroundThe aim of this study was to evaluate the effects of patient positioning on the volume of organs at risk (OARs) in or near the planning target volume (PTV) and the dose distribution in adjuvant or salvage radiotherapy for prostate cancer after prostatectomy.MethodsSeventeen patients who received intensity-modulated radiation therapy (66 Gy in 33 fractions) as adjuvant or salvage therapy after prostatectomy were evaluated. All patients underwent CT scans in both the prone (on a belly board) and supine positions. The target volumes and OARs were delineated on each CT series. The planning target volume (PTV) was extended in every direction to generate the PTV + 0.5 cm, PTV + 1 cm, PTV + 2 cm, PTV + 3 cm, and PTV + 4 cm values. The volumes of the OARs overlapping with the PTV and the extended target volumes in the prone and supine position were compared using the Wilcoxon signed-rank test. Dose-volume histogram (DVH) parameters in the prone and supine position were compared using the paired t-test.ResultsThe mean overlapping volumes of the small intestine for each of the PTV values were as follows (prone position vs. supine position [mean ± SD]): PTV, 1.5 ± 5.5 cm3 vs. 7.9 ± 15.7 cm3 (P = 0.028); PTV + 0.5 cm, 2.6 ± 8.9 cm3 vs. 12.1 ± 22.6 cm3 (P = 0.028); PTV + 1 cm, 3.5 ± 11.4 cm3 vs. 17.1 ± 29.8 cm3 (P = 0.028); PTV + 2 cm, 5.6 ± 14.5 cm3 vs. 26.8 ± 46.9 cm3 (P = 0.028); and PTV + 3 cm, 9.0 ± 17.4 cm3 vs. 36.5 ± 63.2 cm3 (P = 0.019), respectively. Some of the overlapping volumes of the rectum and bladder were significantly smaller in the prone position. On the other hand, when the target volume was extended by ≥2 cm, the overlapping volumes of the femurs were significantly larger in the prone position. V15 of the rectum and mean dose and V65 of the bladder were significantly lower in the prone position.ConclusionsThis study indicated that the volumes of the small intestine, rectum, and bladder in or near the PTV decreased when the patient was placed in the prone position on a belly board in postoperative radiotherapy for prostate cancer. The dose distribution seemed superior in the prone position to the supine position.